Spinal Muscular Atrophy SMN1 Billy Baader - Genetics 677 Medline Plus (2009) Spinal Muscular Atrophy retrieved Feb 3, 2009 from:

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Presentation transcript:

Spinal Muscular Atrophy SMN1 Billy Baader - Genetics 677 Medline Plus (2009) Spinal Muscular Atrophy retrieved Feb 3, 2009 from: Gubitz et al. The SMN Complex. Experimental Cell Research(2004) 296: 51-56

What is SMA? Neuromuscular Disease Inactivated Muscle Communication Weak and eventually atrophied muscles Death is inevitable Characterized by time of onset and severity

Severity and Statistics Type I Acute - <6 months after birth Type II Intermediate - age months Type III Mild - 18 months - early adulthood Type IV Adult Onset - adulthood 1 in Americans are carriers 1 in 10,000 infants effected Most deadly recessive genetic disease among infants Retrieved from:

Cause of SMA - SMN1 Deletion or a mutation of the SMN1 gene leads to SMA SMN1 encodes Survival of motor neuron protein 1 Functions in snRNP biogenesis and mRNA processing Problem is in the anterior horn cells

Spinal Cord Retrieved from:

SMN1 Gene + Protein 28,050 base pairs 294 aa 9 exons SMN2 Spinal Muscular Atrophy Foundation (2009) About SMA retrieved from: Retrieved from:

SMN Complex Gubitz et al. The SMN Complex. Experimental Cell Research(2004) 296: 51-56

Protein Network (Homo Sapiens) Retrieved from:

Protein Network (Mus Musculus) Retrieved from:

Phylogeny Retrieved from:

Homologs 1. SMN1, Pan troglodytes (Chimpanzee) survival of motor neuron 1, telomeric 2. SMN, Canis lupus familiaris (Dog) survival motor neuron 3. SMN, Bos taurus (Cow) survival motor neuron 4. Smn1, Mus musculus (Mouse) survival motor neuron 1 5. Smn1, Rattus norvegicus (Rat) survival motor neuron 1 6. SMN, Gallus gallus (Rooster) survival motor neuron 7. smn1, Danio rerio (Zebrafish) survival motor neuron 1 Percent Identity: DNA: 99.4 Protein:100 DNA: 90.8 Protein: 89.4 DNA: 88.2 Protein: 85.2 DNA: 83.5 Protein: 83.3 DNA: 82.1 Protein: 81.2 DNA: 67.1 Protein: 64.8 DNA: 61.2 Protein: 59.0

Protein Domain: Tudor Retrieved from: Huang, Y. et al. (2006) Science. 312(5774): PDB: 2GFA Protein-protein Interactions RNA metabolism Not fully understood

Mystery of SMA Why low levels of SMN protein in the cells of SMA patients lead to the specific loss of motor neurons remains a central question in this field. SMN may be involved in the transport of specific mRNA molecules in motor axon. However, whether the clinical symptoms of SMA are caused by deficiencies in functions of SMN that are specific to the motor neuron or common to all cells but at higher demand in this cell type must still be resolved.

Future Possibilities Yeast Two Hybrid –Neural vs. other tissues Microarrays of gene expression in different tissues Mice should be good model organisms to research SMA Retrieved from:

Questions

References 1. Spinal Muscular Atrophy Foundation (2009) About SMA retrieved Feb 3, 2009 from: d=32&Itemid=32 2.Medline Plus (2009) Spinal Muscular Atrophy retrieved Feb 3, 2009 from: 3.eMedicine (2009) Spinal Muscular Atrophy retrieved Feb 3, 2009 from: 4.Fight SMA What is Spinal Muscular Atrophy retrieved Feb 3, 2009 from: